Microcalcifications (MCs) are routinely used to detect breast cancer in mammography. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. We combine histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and generate micron-scale resolution correlative maps of crystalline phase, trace metals, particle morphology, and organic matrix chemical signatures within high grade ductal carcinoma in situ (DCIS) and invasive cancer. We reveal the heterogeneity of mineral-matrix pairings, including punctate apatitic particles (<2 μm) with associated trace elements (e.g., F, Na, and unexpectedly Al) distributed within the necrotic cores of DCIS, and both apatite and spheroidal whitlockite particles in invasive cancer within a matrix containing spectroscopic signatures of collagen, non-collagen proteins, cholesterol, carotenoids, and DNA. Among the three DCIS samples, we identify key similarities in MC morphology and distribution, supporting a dystrophic mineralization pathway. This multimodal methodology lays the groundwork for establishing MC heterogeneity in the context of breast cancer biology, and could dramatically improve current prognostic models.
Introduction: The purpose of this study was to validate Bosnian translation of disease specific quality of life measure MSQoL-54 which is widely used in practice. Material and Methods: Previously translated and culturally adopted MSQoL-54 questionnaire used in this study has been provided and licensed by Optum Inc. The questionnaire was validated in 62 MS patients seen at Neurology clinic at University Clinical Center Sarajevo, during April 2016 until May 2016. Internal reliabilities of Bosnian version MSQoL-54 were assessed for multiple item scales by using Cronbach’s alpha coefficient. Clinical validity was assessed comparing means of the two summary MSQoL-54 scores by the EDSS score. Pearson’s (r) correlation coefficient was used to investigate the relationship between the composite scores and the main clinical and demographic variables. Results: Patients’ participation was satisfactory and all scales fulfilled the usual psychometric standards. Highly significant inverse relationship was found between both composite scores and clinical characteristics of the disease and the EDSS. The lowest internal consistency reliability is found on social function scale (0.743), overall quality of life (0.782) and pain (0.833). The highest internal consistency reliability is found on role limitations due to physical problems (0.959), physical health (0.962) and role limitations due to emotional problems (0.966). The mean value of MSQoL-54 PHC (Physical Health Composite) and MHC (Mental Health Composite) were 49.82±18.90 (36.05-61.38) 51.84±22.22 (34.93-70.20) respectively. Our study has shown that the Bosnian version of MSQoL-54 is easy to administer and well accepted by patients and may be useful as clinical outcome measures in patients with MS.
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near‐normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI‐Quant; n = 11) or aberrant collagen structure (OI‐Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI‐Quant patients and healthy controls, whereas fewer were evident in the OI‐Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research.
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